Improvement of colchicine oral bioavailability by incorporating eugenol in the nanoemulsion as an oil excipient and enhancer

Abstract

The effect of eugenol on colchicine transport across an isolated rat intestinal membrane was studied using an in vitro diffusion chamber system. We found that eugenol increased the absorptive transport of the drug efficiently. The effect of eugenol on intestinal absorption of colchicine in an oral administrative nanoemulsion formulation was also demonstrated in vivo. The colchicine nanoemulsion was prepared with isopropyl myristate, eugenol, Tween80, ethanol and water, and eugenol was used as an oil phase in the formulation; an average particle size of this nanoemulsion was 41.2 ± 7.2 nm. The permeation of colchicine in the nanoemulsion across the intestinal membrane was significantly different from that of the control group (0.2 mM colchicine). Finally, co-administration of eugenol in colchicine nanoemulsion to enhance the colchicine bioavailability was investigated by an oral administration method. After oral administration of colchicine (8 mg/kg) in the form of either the nanoemulsion or in free colchicine solution, the relative bioavailability of nanoemulsion and eugenol–nanoemulsion were enhanced by about 1.6- and 2.1-fold, respectively, compared with free colchicine solution. The procedure indicated that the intestinal absorption of colchicine was enhanced significantly by eugenol in the tested nanoemulsion. All the results suggested that eugenol is an efficient component in an oral administrative formulation for improving the intestinal absorption of colchicine.

Keywords:

• intestinal absorption
• nanoemulsion
• absorption enhancement
• eugenol

Acknowledgements

The work was supported by the Shanghai Municipal Committee of Science and Technology (Grant No. 08DZ1971304) and the National Basic Research Program of China (973 Program), No. 2007CB936004.

Disclosure

The authors declare no conflicts of interest in this work.